Arteriosclerosis, which is induced and progressed by various risk factors, causes thickening of the arterial lumen to interrupt blood flow, resulting in a cardiovascular disease such as aortic aneurysm, angina, myocardial infarction, or cerebral infarction. When the cardiovascular disease becomes severe, the patient may die. Therefore, the patient is desirably subjected to early diagnosis and appropriate treatments. One of the subjective symptoms of patients with the cardiovascular disease is chest pain or discomfort. However, only a small percentage of patients with chest pain or the like actually develop or have a probability of development of the cardiovascular disease. Therefore, the patients are required to be subjected to differential diagnosis by a doctor.
The presence or absence of a cardiovascular disease can be examined precisely by, for example, cardiac catheterization or angiography. However, it is necessary to insert a catheter into the vessel in the cardiac catheterization and to introduce a contrast dye into the vessel in the angiography, resulting in heavy burdens on both a subject to be examined and a healthcare professional. Further, cost burdens for the examination may increase medical costs spent by the country or the like. Therefore, it is difficult to conduct a thorough examination for all patients with subjective symptoms.
Therefore, prior to the thorough examination, the patients are subjected to differential diagnosis mainly through history taking. However, the differential diagnosis based on the history taking is insufficient in accuracy because of its large dependence on experiences of doctors.
Previous studies reported that biomarkers such as troponin T and high-sensitivity C-reactive protein (CRP) were useful in examinations for a cardiovascular disease. An increased blood troponin T level enables highly accurate diagnosis of acute myocardial infarction. However, it is difficult to examine the presence or absence of a non-severe cardiovascular disease with troponin T. In addition, high-sensitivity CRP is non-specific because the high-sensitivity CRP level increases in patients with various inflammatory diseases. Therefore, high-sensitivity CRP is not a reliable biomarker that is used in routine differential diagnosis for a cardiovascular disease even at the present day when measurement environments are sufficient.
Therefore, a method capable of examining a cardiovascular disease readily with high accuracy is now required.
Cyclophilin A (CyPA) protein encodes a chaperon protein that binds to cyclosporin. A previous study suggests that cyclophilin A protein promotes production of oxidative stress in models of abdominal aortic aneurysm, induced by angiotensin II in ApoE−/− mice, and is essential for generation of models of abdominal aortic aneurysm (Non Patent Literature 1). In addition, it has been reported that cyclophilin A protein is involved in angiostenosis (Non Patent Literature 2), atherosclerosis (Non Patent Literature 3), and increased production of reactive oxygen species (Non Patent Literatures 4 and 5).
However, cyclophilin A protein is known to have various functions such as infection with HIV virus (AIDS) and replication of hepatitis C virus in addition to those described above. In recent years, drug development in the infectious disease field based on such functions has attracted attention. Further, usefulness of cyclophilin A protein as a biomarker for a cardiovascular disease has been unknown heretofore. For example, there has been unknown a correlation between the presence of an actual cardiovascular disease, in particular, human cardiovascular disease, and the concentration of cyclophilin A protein in blood or the like.